Specific point mutations may not accumulate with aging in the mouse
mitochondrial DNA control region.

Song X, Deng JH, Liu CJ, Bai Y.

Department of Cellular and Structural Biology, University of Texas
Health Sciences Center at San Antonio, San Antonio, Texas 78229, United
States.

Increasing evidence suggests that mitochondrial function declines
during aging in various tissues and in a wide range of organisms. This
correlates with an age-dependent large accumulation of specific point
mutations in the mtDNA control region that was reported recently in
human fibroblast and the skeletal muscle. However, it is rather rare to
evaluate aging-related mtDNA mutations in other model animal systems.
In this study, we analyzed mtDNA control regions of brain, skeletal
muscle, heart, and other tissues from aged mice, in search of specific
point mutations. A 948-bp fragment covering the entire mtDNA control
region from various tissues of mice at the age of 25-26 months was
sequenced. The sequence analysis was accomplished with a newly
developed program Mutation Quantifier, which was able to accurately
detect mutations with the frequencies at as low as 3%. Probably due to
the relative shorter life-span, unlike what have been reported in human
mtDNA, our results indicated there might be no significant accumulation
of specific mutations in mouse mtDNA control region during aging.

PMID: 15829427 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&...

MtDNA point mutations are associated with deletion mutations in aged
rat.

Pak JW, Vang F, Johnson C, McKenzie D, Aiken JM.

Department of Animal Health and Biomedical Sciences, University of
Wisconsin-Madison, 1656 Linden Drive, Madison, WI 53706, USA.

The age-dependent accumulation of point mutations in the control region
of human mtDNA has been suggested to contribute to aging processes. We
investigated whether mtDNA point mutations accumulate to detectable
levels in this region of mtDNA from aged Fischer 344 X Brown Norway
F(1) hybrid rats. The control region and a portion of the major arc
region (nucleotides 4386-7707) of the mtDNA were PCR-amplified and
directly sequenced from microdissected single cardiomyocytes and single
skeletal muscle fibers of 36-month old rats. Point mutations were not
observed in these regions of the full-length mtDNA. Point mutations
were, however, associated with deletion mutations, especially in
cardiac cells. Approximately 40% of the deletion mutations identified
in heart contained a point mutation, whereas only 1.9% of deletion
mutations in skeletal muscle contained a point mutation. Point
mutations were located adjacent to the deletion breakpoints and each
point mutation was unique. In aged rats, point mutations are clonally
expanded only when associated with deletion events suggesting that
there are important differences between rats and humans in the
mechanisms that cause mtDNA abnormalities.

PMID: 15763398 [PubMed - in process]

  This may suggest that that humans have a better or tighter copy
number control. Deletion mutations and clonal expansions occur in in
human cells with relaxed copy number control but apparently not
normally as in mice . If this is in fact true then this could
presumably account for the longer lifespans and decreased ROS of humans
in relation to mice.

Tim